Method of using a topical application device

ABSTRACT

A breathable electrical heater element for a topical application device such as a wound dressing or a therapeutic heating pad is disclosed. The heater element is formed by photochemically etching a track pattern onto a porous metallised fabric (e.g. nickel coated woven polyester). The heater element has a skin or wound contact layer laminated to the front face of the heater element. An adhesive layer is laminated to the back face of the heater element. The adhesive layer forms an overhang to provide an adhesive border around the wound contact layer to adhere the device to the skin of a patient. Therapeutically active drugs (optionally microencapsulated) may be incorporated into the skin or wound contact layer. Operation of the heater element causes the skin or wound contact layer to release the active drugs to the skin or wound of the patient. Appropriate control of the temperature of the heater element allows control of the release of the active drugs.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional continuation application of applicationSer. No. 10/558,851, filed Aug. 24, 2006, now U.S. Pat. No. 7,767,936the entire contents thereof is incorporated herein by reference.

BACKGROUND TO THE INVENTION

1. Field of the Invention

The invention relates to a therapeutic heater element. In preferredembodiments, the invention relates to a breathable, porous, flexiblefabric heater that is incorporated into heating pads for vasodilationtherapy or pain relief and/or wound dressings and a thermally activateddrug and chemical delivery system.

2. Related Art

The use of direct heating for the therapeutic treatment of joint andmuscular pain in humans is a known practice and is claimed to bringsignificant relief to patients (U.S. Pat. No. 5,534,021). Theapplication of heat directly to wound sites has also been reported tocontribute to improved wound management and healing (WO03/039417). Knownthermal therapies have relied on the use of:

-   -   a) IR metal radiators (which can be applied to the patient in        the form of a wrap and which may be disposed of after use);    -   b) electrical infra-red heating devices;    -   c) carbonised fibre heater elements; and    -   d) exothermic materials.

Furthermore, it is also known to deliver drugs through the skin of apatient using a heated contact pad, as disclosed in U.S. Pat. No.6,613,350.

SUMMARY OF THE INVENTION

The present inventor has realised that known electrical heating deviceshave some drawbacks and limitations that limit their potential use intherapeutic applications. These include high cost, lack ofbreathability, brittleness, inflexibility, restricted portability and alack of disposability. Accordingly, the present invention has been madein order to address these drawbacks and limitations, and preferably toreduce, ameliorate or even overcome them.

The present inventor has realised that there is a need for acost-effective, disposable electrical heating system. Such a heatingsystem may find use in deep-heat therapeutic muscular and joint paintreatment and/or in wound-care, where thermal regulation of the woundsite is considered beneficial. In addition, the heating system may finduse in utilising thermal regulation to deliver drugs and/or othermedicinal chemicals to the wound site. It may also find use in assistingin vasodilation prior to cannulation, for example. This is of particularimportance in paediatric medicine.

Accordingly, in a first aspect, the present invention provides atherapeutic heater element formed from flexible metallised fabric, fortopical application for treatment.

Typically, the heater element is formed by photochemical etching ofmetallised fabric.

Details of the construction, manufacture and heating performance of asuitable flexible, porous etched metallised fabric heater are describedin WO03/053101, the content of which is incorporated by reference in itsentirety. WO03/053101 claims priority from UK Patent Application No.0228999.9, filed 14 Dec. 2001.

Preferably, the heater element has termination pads. These are at theend of the etched track and allow connection of the heater element to apower source/control system.

It is contemplated that the present invention is of use both in atherapeutic heat-treatment topical application and/or vasodilationdevice (e.g. a pad) and in a wound topical application and/orvasodilation device (e.g. dressing). Both of these devices are thereforepreferred aspects of the invention.

Preferably, the heater element is porous. This allows the pad ordressing to be breathable.

An advantage of using an electrical heating system rather than achemical heating system (e.g. using the heat generated by an exothermicreaction) is that the temperature of the heating system can be regulatedand controlled either manually by the patient or medical practitioner orautomatically by suitable control circuitry. Preferably, the topicalapplication for treatment includes a power source (such as a battery)for connection to the heater element. Optionally, it may also includecontrol circuitry for controlling the temperature of the application.

Preferably, the heater element is held within either a partially orfully integrated textile or nonwoven fabric laminate. The device may bedesigned to be wearable, conformable and discrete in use. Preferably,the device is capable of controlling the microclimate between the heaterand the body.

Preferably, the device has at least one therapeutic agent for deliveryto a subject. The delivery of the therapeutic agent or agents to thesubject may be assisted by operation of the heater element to generateheat. For example, the device may be a drug-delivery system for woundmanagement for enabling the administration of therapeutic preparationsto a patient (e.g. growth factors and ointments). The therapeutic agentmay be a pain-relieving formulation (e.g. ibuprofen or similar) or itmay be a vasodilation formulation (e.g. EMLA or similar).

In a preferred approach, the therapeutic agent or agents of interest aremicroencapsulated in microcapsules. Suitable microcapsules are thosethat melt at a particular initiation temperature. Alternativemicrocapsules are those that allow diffusion of the active chemicalsthrough their walls to effect a slow release mechanism from the device.By appropriate temperature control, the heater element may then be usedto initiate the delivery of such active chemicals or agents. It will beunderstood that by the encapsulation of various active agents and theuse of microcapsules having different thermal characteristics, thetiming of the delivery of each agent can be controlled as required.

In a preferred embodiment, an etched breathable metallised fabricheating element is laminated or otherwise attached to a nonwoven ortextile fabric, which forms part of a skin contact pad or wounddressing. The heater element may be a component in a bilaminate ormultilaminate structure as required. The porous heater element with anappropriate track pattern may be encapsulated in a suitable continuouspolymer to produce a breathable, water-proof, flexible, thin heaterelement, which by the use of a suitable connector to a portable batterycan be powered to deliver significant thermal energy to the wearer.Preferably, the thickness of the heater element is less than 1 mm (e.g.<1.0 mm).

During manufacture of the heater element, it is possible to select thewidth, length and shape of the etched-track pattern. The selection canbe varied widely to optimise the heater element performance in use or toprovide differential heating across the heater element in use.

Preferably, the heater element is capable of being controlled toregulate the rate of heating and/or the maximum heat output. Regulationcan be achieved either manually by the wearer via a suitable controldevice or automatically by the heater system itself (which may bepre-programmed as necessary).

The heater element may therefore be controllable to provide atime-dependent heating profile (e.g. a gradual increase in temperatureor a step-wise increase in temperature) during use. This is ofparticular use where more than one active agent is contained in thetopical application. Each active agent may be selected in order to bereleased at a particular temperature. Thus, the control of thetemperature of the device allows the control of the release of theactive drug to the subject.

The preferred thin and flexible characteristics of the heater elementminimise stiffening of the pad or dressing and ensure it is able toconform to the shape of different sites and extremities on the bodywhere heat treatment is needed.

Preferred features of a therapeutic heating pad according to anembodiment of the invention will now be set out.

A heating pad preferably has a skin contact layer selected from nonwovenand/or other textile structures that are known skin contact layermaterials (e.g. hydroentangled, thermal bonded or needlepunchednonwovens may be used as well as knitted, woven, mesh fabrics orcontinuous or perforated films). The pad may be breathable and may alsobe absorbent due to the hydrophilic nature of a polymer composition (asrequired).

The heater element may be laminated to the skin contact layer or to abacking layer using a thermoplastic web material. Such materials aretypically fibrous and have a high degree of open porosity. Typicalthermoplastic webs soften when heated (e.g. to around 130° C.). Pressuremay be applied to speed up the softening of the material. Typically, thethermoplastic web material is located between the heater element and theskin contact layer. This arrangement is then heated and pressed so thatthe thermoplastic web is softened and deformed to adhere the heaterelement to the skin contact layer to form a laminate.

Preferably, the flexible, porous heater element is laminated orotherwise attached to the back of the contact layer in such a way thatheat energy can be transferred through the contact layer by themechanisms of conduction and/or convection. A retaining layer or backinglayer (having an approved skin contact adhesive) may be applied over thelaminate to fix its position on the patient. Alternatively, the adhesivelayer may be laminated to the reverse side of the heater element to forma fully integrated tri-laminate structure.

Suitable electrical connection for powering the heater element may beprovided at the extremity of the pad. Preferably, the connection iscapable of disconnection from the power source after use.

Preferably, the heating pad is thin and conformable and when fixed inplace by a suitable adhesive retaining layer can be operated and worn bythe patient without restricting their normal activities. Differentialheating of the patient over the area of the heater element can beachieved by selecting an appropriate element track pattern duringmanufacture and/or by suitable adjustment of the temperature controlprovided to the heater element.

Preferably, the pad includes means for administering therapeutic drugsor chemicals to the patient through the skin contact pad by appropriateregulation of the temperature of the heater element to initiate therelease of encapsulated or non-encapsulated active chemicals.

In a preferred embodiment a liquid permeable nonwoven skin contact pador perforated film is pre-impregnated or coated with microencapsulatedtherapeutic drugs or chemicals. Preferably, the delivery of thesefunctional components is achieved by diffusion through the walls of themicrocapsules or by melting of the microcapsules (induced by the heaterelement), which releases the encapsulated components. By applyingdifferent microencapsulated drugs or chemicals in microcapsules havingdifferent thermal properties it is possible to deliver the active drugsor chemicals at different intervals by adjusting the heater elementtemperature.

Suitable materials for encapsulating suitable agents include lipids suchas wax, paraffin, tristearin, stearic acid, monoglycerides,diglycerides, beeswax, oils, fats and hardened oils.

In the case where the active agent is ibuprofen, it is preferred theagent is encapsulated within wax microspheres, according to knownencapsulation techniques.

In the case where the active agent is EMLA (a mixture of active agents)it may be preferred not to microencapsulate the agent.

Preferred features of a wound dressing according to an embodiment of theinvention will now be set out.

The potential benefits of heating a wound site are set out in U.S. Pat.No. 6,423,018 and U.S. Pat. No. 6,436,063. These include increasedcutaneous and subcutaneous blood flow and increased immune systemfunctions both humoral and cell mediated, including increased migrationof white blood cells and fibroblasts to the site.

The microclimate of the wound-site (including temperature and moisturevapour), are important in the process of wound healing and can beinfluenced by the type of wound dressing used (e.g. occlusive ornon-occlusive). Whilst a moist wound site has been shown to bebeneficial for healing, excessive wetting out of the wound and thesurrounding area can cause tissue maceration and an increasedprobability of infection. It is anticipated that the ability to controlthe temperature of the wound-site may also provide a means of regulatingthe relative humidity and control the potential for condensation, whichcan lead to maceration. Wound site microclimate control is preferablyachieved by the present invention.

It is preferred that, in use, the dressing provides a means forregulating the temperature of the wound site to maintain a meantemperature (e.g. normal skin temperature). The availability of atemperature/concentration gradient across the wound contact layer alsoprovides a useful means for the delivery of drugs and other chemicals tothe wound site from within the dressing.

Preferably, the breathable fabric heater element is incorporated into astandard disposable wound dressing architecture, which in simple formconsists of a wound contact layer (e.g. knitted or woven gauzes,nonwoven fabrics or films) to which a porous flexible heater element isattached to the reverse side. More preferably, the fabric heater elementis incorporated in such a way that there is substantially no possibilityof body fluids coming into contact with its surface, which mightotherwise induce an immunological response depending on the surfacechemistry of the element.

Preferred embodiments of the invention include composite andisland-dressing structures. Typically, these have a wound contact layer(e.g. a low adherent film) attached to an absorbent or superabsorbentcore. In turn this may be covered by a moisture vapour permeableretaining layer, which may have an approved skin-contact adhesive aroundits inner surface to allow its fixation to the patient. In suchcomposite dressings, the flexible heater element is preferablyincorporated above the absorbent core rather than immediately above thewound contact layer. Alternatively, a breathable film may be used toseparate the absorbent core from the heater element. This may bepreferable when high levels of wound exudates are produced (e.g.pressure sores).

The flexible metallised fabric may be shaped so as to provide terminalsfor electrical connection of tracks formed on the fabric at an elongateflexible tail portion of the fabric. In this way, the heat-generatingtracks may be connected to a suitable power supply via the terminals atthe tail portion. This avoids the need for conventional wires to betrailed through the dressing or pad from the power supply to the fabric.

Preferably, drugs and/or other functional chemicals are deliverable tothe wound site via the wound contact layer. Typically, the delivery ofthese agents is triggered by the heat energy produced by the fabricheater element. In one embodiment, drugs and/or chemicals such asantimicrobials, ointments, growth factors, steroids and othertherapeutic preparations are encapsulated in microcapsules, and aredelivered by diffusion through the wall or by thermal degradation ormelting of the microcapsule. The microencapsulated drugs and chemicalsmay be applied to the dressing by any known methods e.g. by coating orsaturation impregnation.

The microcapsules may be applied directly to the wound contact layer orto other layers in the dressing depending on its particular design. In apreferred embodiment, the heater element is used to initiate complete orpartial melting (fusion) of the microcapsule wall to release the activecomponents to the wound site. Using this temperature-induced approach todrug delivery, it is therefore possible to administer various topicaltreatments by applying different microencapsulated drugs and chemicalson to the dressing and by using microcapsules having different thermalproperties.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic sectional view of a thermal treatment padaccording to an embodiment of the invention.

FIG. 2 shows a schematic sectional view of a laminated structureaccording to an embodiment of the invention.

FIG. 3 shows a schematic sectional view of a wound dressing according toan embodiment of the invention.

FIG. 4 shows a schematic plan view of a heater element for use in thewound dressing of FIG. 3.

FIG. 5 shows a schematic sectional view of a thermal treatment padshowing microencapsulated therapeutic agents in a skin contact layeraccording to an embodiment of the invention.

FIG. 6 shows a schematic sectional view of a laminated structure showingmicroencapsulated therapeutic agents in a wound contact layer accordingto an embodiment of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 shows a schematic view of a thermal treatment pad 10 according toan embodiment of the invention. Skin contact layer 15 has disposed aboveit a flexible, breathable metallised fabric heater element 14 that isdescribed in more detail below. The pad is held together and affixed toa patient's skin by adhesive layer 12.

FIG. 2 shows a schematic view of a laminated structure including a woundcontact layer 16 laminated to heater element 14. The wound contact layeris, for example, a woven gauze material of low adherence that is knownin the art of wound dressings. Alternative materials for the woundcontact layer include a low adherence film, mesh or nonwoven fabric(including absorbent and superabsorbent compositions).

FIG. 3 shows the laminated structure of FIG. 2 incorporated into anisland wound dressing. Adhesive retaining layer 18 is laminated to theback surface of the heater element 14 and extends forwardly to besubstantially flush with the front surface of wound contact layer 16.When applied over a wound of a patient, the adhesive retaining layer 18adheres to the patient's skin surrounding the wound to retain thedressing with respect to the wound and the patient.

FIG. 4 shows a plan view of the heater element 14 used in the wounddressing of FIG. 3. A similar heater element is also suitable for use inthe thermal treatment pad 10 of FIG. 1. In FIG. 4, a metallic track 22is etched from a piece of porous metallised fabric (e.g. nickel-coatedwoven polyester) to leave track 22 and etched fabric 20. The pattern ofthe track is such that terminal connection points 24, 26 are formed, forconnection to a power source such as a battery and suitable controlcircuitry to control/limit the heat output of the heater element 14 inuse.

The heater element is formed by taking a nickel coated polyester wovenfabric and cutting it to the shape required for the thermal treatmentpad or wound dressing after the formation of the heater track pattern byphotochemical etching, as described below. A suitable material is thecommercially available metallised fabric Metalester (Registered TradeMark), a woven electroless nickel plated polyester mesh. Such fabricsare available with a variety of thread thicknesses, thread spacings,type of weave and weight of nickel. Threads may typically have adiameter within the range 24 to 600 micrometers (microns), a threadcount of between 4 and 737 per cm, and a metal coating of varying weightper square meter.

Suitable fabrics may be coated with a continuous layer of metal aftermanufacture, for example by sputtering, by chemical reduction or byelectro-deposition, which results in total encapsulation of all thethreads of the mesh in metal. In an alternative mesh, the individualwarp and weft threads may be metallised prior to fabric production, forexample by sputtering, by chemical reduction or by electro-deposition.

After selecting the desired metallised fabric, the desired track patternis photochemically etched from the fabric. This is done by firstdesigning and generating a suitable phototool, in a way well known tothe skilled person. Next, the fabric is mounted onto a hinged frame ofbrown styrene board, so that the otherwise flimsy fabric can be morereadily handled. The fabric is then cleaned with a commercial surfacecleaning agent to assist in the adhesion of the photoresist. Then, thephotoresist is applied, typically by dip-coating the fabric into aliquid photoresist to ensure application of the photoresist to all partsof the fabric by immersion.

Next, the fabric is exposed to a suitable image pattern of ultravioletlight from the phototool. This image is developed. The unrequired metalis then progressively etched away. Then, the photoresist is removed toleave the required metallic track shape for the heater element, as shownin FIG. 4. The heater element is then cut to the required shape.

The heater element is fixed to a suitable skin or wound contact layer.Suitable materials will be known to the person skilled in the art. Anexample of a fixing method of the heater element is by the interpositionof a thermoplastic web between the heater element and the skin or woundcontact layer.

A suitable thermoplastic web material is the melt-spun interliningmaterial Vilene (registered trade mark) U25 supplied by FreudenbergNonwovens Interlining Division (part of Freudenberg Vliesstoffe KG). TheU25 grade is made from 100% polyamide and has a random web structure anda weight of 25 grams per square meter. The material softens and fuseswhen heat is applied at about 130° C. for about 10 seconds with apressure of 15-30 N/cm². The web has a high degree of open porosity andso allows the lamination between the skin or wound contact layer and theheater element to give rise to a breathable structure.

Although not shown in FIG. 4, it is preferred that the heater elementhas a fully flexible tail portion extending away from the main part ofthe heater element, the tail portion carrying the connection tracks forthe heater element (these connection tracks having lower resistance tothe heat-generation tracks of the heater element) to terminals formed atthe end of the tail portion. In this way, a power supply can beconnected to the terminals without disturbing the dressing or pad.

A suitable power supply (not shown) is supplied by Mpower BatteriesLimited, consisting of 2×3.6 V lithium ion batteries. Suitable controlcircuitry is also available from the same source. See also the controlcircuitry disclosed in WO 03/039417.

Microencapsulated drugs 17 can be incorporated into the skin contactlayer 15, as seen in FIG. 5, or into the wound contact layer 16, as seenin FIG. 6. The microcapsules 17 used are of the type that release theircontents due to heat activation, e.g. due to melting of the capsule wallmaterial or thermal degradation of the capsule wall material ordiffusion of the content of the capsule through the wall due toincreased temperature. In particular, microcapsules 17 that graduallyrelease their content on heating are preferred.

In a preferred embodiment, microencapsulated ibuprofen is used, such asis disclosed in the following documents: Adeyeye, C. M., and Price, J.C., “Development and Evaluation of Sustained Release Ibuprofen-WaxMicrospheres: I. Effect of Formulation Variables on PhysicalCharacteristics” (Pharmaceutical Research, 8, #11, 1377-1383 (1991)November); Adeyeye, C. M., and Price, J. C., “Development and Evaluationof Sustained Release Ibuprofen-Wax Microspheres: II. In VitroDissolution Studies” (Pharmaceutical Research, 11, #4, 575-579 (1994));Adeyeye, C. M., and J. C. Price, “Chemical, dissolution stability andmicroscopic evaluation of suspensions of ibuprofen and sustained releaseibuprofen-wax microspheres” (Journal of Microencapsulation, 14, (1997)).

In another embodiment, the invention has particular application toassisting vasodilation in venipuncture and IV cannulation.

Venipuncture for laboratory tests and intravenous (IV) insertion arecommon medical procedures, and many patients with chronic illness havethese procedures repeatedly performed during the course of theirtreatment. Needle insertion is the most frightening and bothersomemedical procedure particularly for children. Studies have shown thatchildren's previous distress during medical procedures is a predicatorof future distress. Some children develop needle phobia that isextremely difficult to treat.

Topical anaesthesia creams have been developed to minimize thediscomfort of venipuncture and many children's hospitals have adoptedthe use of eutectic mixture of lidocaine and prilocalne (EMLA) as partof their pain management standard of practice. Numerous studies haveshown that EMLA decreases pain sensation for children during needlesticks (see, for example, Robieux I., Kumar R., Radhakrishnan S., KorenG., “Assessing pain and analgesia with a lidocaine-prilocalne emulsionin infants and toddlers during venipuncture” (J. Pediatr. 1992; 118:971-973). It has been found that the anaesthetic is more effective forsimple venipuncture than for IV cannulation.

EMLA cream (lidocaine 2.5% and prilocalne 2.5%) is an emulsion in whichthe oil phase is a eutectic mixture of lidocaine and prilocalne in aratio of 1:1 by weight. This eutectic mixture has a melting point belowroom temperature and therefore both local anaesthetics exist as a liquidoil rather than as crystals. EMLA is available as a cream but alsoincorporated into an occlusive dressing having a laminate backing, anabsorbent cellulose disc, and an adhesive tape ring.

In use, the EMLA cream is applied liberally to the skin of the back ofthe hand. An occlusive dressing is then applied to push the creamagainst the skin and to prevent the cream from leaking away from therequired area. The cream must be left in place for between 30 minutesand 1 hour to have the desired anaesthetic effect.

It is found that EMLA may constrict the veins under the skin where it isapplied. This makes IV cannulation more difficult.

Incorporation of the heater element into the dressing or pad allows thedressing or pad to be heated to help to vasodilate the veins ofinterest. Accordingly, the heater element is of assistance in overcomingat least one drawback of using EMLA.

Furthermore, the incorporation of the heater element into the dressingor pad allows the heat generated by the heater element to encourage thedeeper and faster transfer of drug into the skin of the patient. Thisallows a suitable local anaesthetic effect to be achieved morecompletely and more fully in a faster time. This is of direct use inpaediatric medicine, as mentioned above, due to the difficulty that canbe encountered with the slow effects of EMLA in normal operation.

The embodiments above have been described by way of example.Modifications of these embodiments, further embodiments andmodifications thereof will be apparent to the skilled person on readingthis disclosure and as such are within the scope of the invention.

The invention claimed is:
 1. A method of operation of a topicalapplication device for topical application of a therapeutic treatmentincluding vasodilation, comprising the steps of: providing a heatgenerating layer; the heat generating layer including a metallisedsubstrate of porous fabric having a plurality of components, selectedfrom the group consisting of yarns, fibers and threads, eachencapsulated in metal wherein the metal on the metallised substrate ofporous fabric is photochemically etched by selectively etching out metalencapsulated about the plurality of components of metallised substrateof porous fabric to create at least one electrical heat generatingcircuit with first portions of the porous fabric being encapsulated withmetal and second portions of the porous fabric not being encapsulatedwith metal; heat being generated by the first portions of the porousfabric; providing a contact layer having at least one therapeutic agenttherein for delivery to a subject; adhering the heat generating layer tothe contact layer; running electricity through the at least oneelectrical heat generating circuit to provide heat output; anddelivering the at least one therapeutic agent to the subject uponproviding the heat output to the contact layer.
 2. The method of claim1, further comprising the step of: controlling the heat output by athermal regulation device.
 3. The method of claim 2, wherein the thermalregulation device is programmable.
 4. A method according to claim 1,further comprising the steps of: providing more than one type oftherapeutic agent contained in different types of microcapsules, havingdifferent thermal characteristics, within the contact layer; timing thedelivery of each of the more than one type of therapeutic agentaccording to a predetermined schedule due to the thermal characteristicsof the microcapsules.
 5. A method according to claim 1, furthercomprising the steps of: providing more than one type of therapeuticagent contained in the same type of microcapsule within the contactlayer; timing the delivery of each of the more than one type oftherapeutic agent according to a predetermined schedule due to thethermal characteristics of the microcapsules.
 6. A method according toclaim 1, further comprising the steps of: providing at least one type oftherapeutic agent contained within the contact layer; timing thedelivery of the at least one type of therapeutic agent according to apredetermined schedule.